American Indians (AI) have the highest smoking rates of any ethnic group in the US (40.8%), followed most closely by African Americans (24.3%) and Whites (23.6%). Additionally, AI women are the only group in whom smoking prevalence has increased over the past two decades, from 34.1% to 40.9%. Smoking rates among AI smokers vary by region and are highest in the Northern Plains 44.1%, and lowest in the Southwest 21.2%. AI smokers also have more difficulty quitting smoking compared to other ethnic groups, evidenced by their significantly lower quit ratios and are among the least successful in maintaining long term abstinence. While health disparities like these have existed for years among AI, the epidemiology of smoking and nicotine dependence has not been optimally described among this underserved population. Our prior work developing a smoking cessation program has revealed that although very high numbers of AI smoke, they typically smoke one-half the number of cigarettes per day compared with a smoker in the majority culture. We have also observed a younger age of initiation. As such, we now propose a formal investigation to understand these patterns. Such factors relating to tobacco use, nicotine dependence and metabolism maybe different between AI and the general U.S. population, and even among AI subgroups. These possible differences have not been previously investigated and must be studied if we are to make significant inroads in developing culturally relevant smoking prevention and cessation strategies for this population. Our overarching thematic hypothesis is that the susceptibility of AI to cigarette smoking and nicotine dependence and its consequences has both an underlying nicotine metabolism component as well as psychosocial, cultural, and environment causes. We are well-positioned to explore this issue for the first time in this population. Our objective is to establish a cohort of AI tribal college/university students to determine the predictors of smoking initiation (non-use to experimentation) and progression (experimentation to established use).